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Can multicellular life be distinguished from single cellular life on an exoplanet? We hypothesize that abundant upright photosynthetic multicellular life (trees) will cast shadows at high sun angles that will distinguish them from single cellular life and test this using Earth as an exoplanet. We first test the concept using unmanned aerial vehicles at a replica moon-landing site near Flagstaff, Arizona and show trees have both a distinctive reflectance signature (red edge) and geometric signature (shadows at high sun angles) that can distinguish them from replica moon craters. Next, we calculate reflectance signatures for Earth at several phase angles with POLDER (Polarization and Directionality of Earth's reflectance) satellite directional reflectance measurements and then reduce Earth to a single pixel. We compare Earth to other planetary bodies (Mars, the Moon, Venus and Uranus) and hypothesize that Earth's directional reflectance will be between strongly backscattering rocky bodies with no weathering (like Mars and the Moon) and cloudy bodies with more isotropic scattering (like Venus and Uranus). Our modelling results put Earth in line with strongly backscattering Mars, while our empirical results put Earth in line with more isotropic scattering Venus. We identify potential weaknesses in both the modelled and empirical results and suggest additional steps to determine whether this technique could distinguish upright multicellular life on exoplanets.
Severe mental illnesses such as schizophrenia and mood disorders have a major impact on public health. Disease prevalence and phenotypic expression are the products of environment and gene interactions. However, our incomplete understanding of their aetiology and pathophysiology thwarts primary prevention and early diagnosis and limits the effective application of currently available treatments as well as the development of novel therapeutic approaches. Neuroimaging can provide detailed in vivo information about the biological mechanisms underpinning the relationship between genetic variation and clinical phenotypes or response to treatment. However, the biological complexity of severe mental illness results from unknown or unpredictable interactions between multiple genetic and environmental factors, many of which have only been partially identified. We propose that the use of epidemiological principles to neuroimaging research is a necessary next step in psychiatric research. Because of the complexity of mental disorders and the multiple risk factors involved only the use of large epidemiologically defined samples will allow us to study the broader spectrum of psychopathology, including sub-threshold presentation and explore pathophysiological processes and the functional impact of genetic and non-genetic factors on the onset and persistence of psychopathology.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
A multitude of risk/protective factors for anxiety and obsessive-compulsive disorders have been proposed. We conducted an umbrella review to summarize the evidence of the associations between risk/protective factors and each of the following disorders: specific phobia, social anxiety disorder, generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder, and to assess the strength of this evidence whilst controlling for several biases.
Publication databases were searched for systematic reviews and meta-analyses examining associations between potential risk/protective factors and each of the disorders investigated. The evidence of the association between each factor and disorder was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of cases (>1000), random-effects p-values, 95% prediction intervals, confidence interval of the largest study, heterogeneity between studies, study effects, and excess of significance.
Nineteen systematic reviews and meta-analyses were included, corresponding to 216 individual studies covering 427 potential risk/protective factors. Only one factor association (early physical trauma as a risk factor for social anxiety disorder, OR 2.59, 95% CI 2.17–3.1) met all the criteria for convincing evidence. When excluding the requirement for more than 1000 cases, five factor associations met the other criteria for convincing evidence and 22 met the remaining criteria for highly suggestive evidence.
Although the amount and quality of the evidence for most risk/protective factors for anxiety and obsessive-compulsive disorders is limited, a number of factors significantly increase the risk for these disorders, may have potential prognostic ability and inform prevention.
Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.
A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.
PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31–1.99), ASD: aHR = 2.02 (95% CI 1.45–2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19–1.57), ASD: aHR = 1.46 (95% CI 1.21–1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.
Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.
OBJECTIVES/SPECIFIC AIMS: Given the poor prognosis of HCC and its increasing incidence worldwide, identifying biomarkers of HCC has been an active area of research. While biomarkers are being identified at a rapid pace, many are still in early phases of clinical study and very few have proven clinical utility. The objective of this study is to identify novel biomarkers of HCC and evaluate their clinical utility as predictors of disease development and prognosis with specific emphasis on disease recurrence after liver transplantation. Biomarkers will be identified through GWAS, as well as through analysis of qualitative and quantitative liver traits by magnetic resonance imaging (MRI). These novel biomarkers will then by implemented into risk prediction models aimed to assess an individual’s risk for development of HCC and stratify their level of risk according to predicted disease prognosis. METHODS/STUDY POPULATION: This will be a case-control study, analyzing data from previously created biorepositories from four cohorts of recipients across multiple centers which have undergone liver transplant. First, a GWAS will be performed to identify genetic variant(s). Second, pre-transplant MRI’s will be evaluated using CAVASS software to assess liver quantitative and qualitative traits, including visceral adiposity. Lastly, these findings will be implemented into risk stratification models to assess each individual’s level of risk for development of HCC and for recurrence of HCC after transplant. RESULTS/ANTICIPATED RESULTS: We hypothesize that genetic variant(s) are associated with positive HCV status and the development of HCC. Additionally, we hypothesize that increased visceral adiposity measured by MRI will have an association with recurrence of HCC after transplant. Lastly, we hypothesize that possession of these aforementioned features will be associated with an increased risk of HCC development and recurrence after transplant. DISCUSSION/SIGNIFICANCE OF IMPACT: As more is learned about the nature and reliability of these biomarkers, their potential clinical applications will be revealed. Ideally these proposed risk score models will ultimately be used by clinicians to provide personalized disease management while optimizing the allocation of health care resources. For instance, this may lead to changes in the MRI screening frequency of patients considered to be at high risk for HCC. The ability to diagnose patients early and provide personalized therapies may ultimately result in fewer disease related mortalities in the future.
Cognitive impairment is a core feature of psychotic disorders, but the profile of impairment across adulthood, particularly in African-American populations, remains unclear.
Using cross-sectional data from a case–control study of African-American adults with affective (n = 59) and nonaffective (n = 68) psychotic disorders, we examined cognitive functioning between early and middle adulthood (ages 20–60) on measures of general cognitive ability, language, abstract reasoning, processing speed, executive function, verbal memory, and working memory.
Both affective and nonaffective psychosis patients showed substantial and widespread cognitive impairments. However, comparison of cognitive functioning between controls and psychosis groups throughout early (ages 20–40) and middle (ages 40–60) adulthood also revealed age-associated group differences. During early adulthood, the nonaffective psychosis group showed increasing impairments with age on measures of general cognitive ability and executive function, while the affective psychosis group showed increasing impairment on a measure of language ability. Impairments on other cognitive measures remained mostly stable, although decreasing impairments on measures of processing speed, memory and working memory were also observed.
These findings suggest similarities, but also differences in the profile of cognitive dysfunction in adults with affective and nonaffective psychotic disorders. Both affective and nonaffective patients showed substantial and relatively stable impairments across adulthood. The nonaffective group also showed increasing impairments with age in general and executive functions, and the affective group showed an increasing impairment in verbal functions, possibly suggesting different underlying etiopathogenic mechanisms.
Bipolar and more complex morphologies observed in planetary nebulae have been explained by two principal hypotheses: by the existence of a companion producing a circumstellar disk, by the effects of a magnetic field, or by a combination of both. The polarimetric analysis of these objects could give information about the presence of dust grains aligned with any preferential direction, due to a magnetic field or to the action of radiative torques (RAT). We performed polarimetric observations of some planetary nebulae in order to detect linear polarization and (in the best scenario) to detect the signature of an accretion disk in these objects. We observed in the visual region with POLIMA at the San Pedro Mártir observatory, and with POLICAN the NIR polarimeter in the Guillermo Haro observatory. We present the result of these observations in one of these objects: the PN M2-9.
Diagnosing streptococcal pharyngitis in children on the basis of clinical appearance and throat culture is complicated by high colonisation rates and by the ability of other pathogens to cause clinically similar disease. To characterise the epidemiology of Lancefield Group A, C and G β-haemolytic streptococcus (GAS, GCS and GGS, respectively) in children, we conducted a 2-year prospective study of 307 school children between 7 and 11 years old. GGS and GAS were commonly identified organisms both for silent streptococcal colonisation and symptomatic sore throat, while GCS was uncommonly found. Streptococcal culture positivity at the time of clinical pharyngitis was estimated to reflect true streptococcal pharyngitis in only 26% of instances, with the frequency varying from 54% for children rarely colonised to 1% for children frequently colonised. Numerous GAS emm types were identified, including several types previously associated with severe pharyngitis (e.g. emm types 1, 3 and 28). No severe complications were seen in any child. These data suggest that the clinical diagnosis of streptococcal pharyngitis is likely to remain difficult and that treatment decisions will remain clouded by uncertainty. There remains a need for organism-specific rapid point-of-care streptococcal diagnostic tests and tests that can distinguish between streptococcal colonisation and disease.
A four-year-old Muslim boy was brought to a local Cologne emergency room by his mother, who was concerned about minor bleeding around the site of a circumcision. A District Court there found that circumcision, notwithstanding parental consent or religious motivation, constituted a criminal bodily injury and child abuse. Ultimately, on July 19, 2012 the Bundestag resolved that “Jewish and Muslim religious life be viable in Germany,” and in December a bill was passed that legislatively overrode the ruling of the District Court and recognized circumcision as a non-punishable undertaking when undertaken for religious reasons by someone professionally trained. Two years of rancorous debate revealed a whole range of historical and contemporary fissures. This essay examines the dynamics of the debate and its various outcomes. In particular it asks whether the conflicts generated by practices like male circumcision can in immigrant societies be assimilated to prevailing religious freedom models. The key questions aired were: (1) Germany's relations with its Muslim immigrants; (2) Germany's relations with its fragile Jewish minority; (3) proper weightings of the relationship among parents, child, and state; and (4) the deference owed medical thinking. Immigrant integration, religious freedom, group rights, and the meaning of “enlightenment” all remain sharply contested.
We present the first dedicated study into the phenomenon of ice sails. These are clean ice structures that protrude from the surface of a small number of debris-covered glaciers and can grow to heights of over 25 m. We draw together what is known about them from the academic/exploration literature and then analyse imagery. We show here that ice sails can develop by one of two mechanisms, both of which require clean ice to become surrounded by debris-covered ice, where the debris layer is shallow enough for the ice beneath it to melt faster than the clean ice. Once formed, ice sails can persist for decades, in an apparently steady state, before debris layer thickening eventually causes a reversal in the relative melt rates and the ice sails decay to merge back with the surrounding glacier surface. We support our image-based analysis with a surface energy-balance model and show that it compares well with available observations from Baltoro Glacier in the Karakoram. A sensitivity analysis of the model is performed and confirms the results from our empirical study that ice sails require a relatively high evaporative heat flux and/or a relatively low sensible heat flux in order to exist.
Analysis of in situ neutron powder diffraction data collected for the porous framework material Zn(hba) during gas adsorption reveals a two-stage response of the host lattice to increasing CO2 guest concentration, suggesting progressive occupation of multiple CO2 adsorption sites with different binding strengths. The response of the lattice to moderate CH4 guest concentrations is virtually indistinguishable from the response to CO2, demonstrating that the influence of host–guest interactions on the Zn(hba) framework is defined more strongly by the concentration than by the identity of the guests.
The human pathogenic nematode Strongyloides stercoralis infects approximately 30–100 million people worldwide. Analysis of the adaptive immune response to S. stercoralis beyond descriptive studies is challenging, as no murine model for the complete infection cycle is available. However, the combined employment of different models each capable of modelling some features of S. stercoralis life cycle and pathology has advanced our understanding of the immunological mechanisms involved in host defence. Here we review: (i) studies using S. stercoralis third stage larvae implanted in diffusion chambers in the subcutaneous tissue of mice that allow analysis of the immune response to the human pathogenic Strongyloides species; (ii) studies using Strongyloides ratti and Strongyloides venezuelensis that infect mice and rats to extend the analysis to the parasites intestinal life stage and (iii) studies using S. stercoralis infected gerbils to analyse the hyperinfection syndrome, a severe complication of human strongyloidiasis that is not induced by rodent specific Strongyloides spp. We provide an overview of the information accumulated so far showing that Strongyloides spp. elicits a classical Th2 response that culminates in different, site specific, effector functions leading to either entrapment and killing of larvae in the tissues or expulsion of parasitic adults from the intestine.
Background: Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. Materials and Methods: In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. Results: There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). Conclusions: The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.
In this paper we undertake a quantitative analysis of the dynamic process by which ice underneath a dry porous debris layer melts. We show that the incorporation of debris-layer airflow into a theoretical model of glacial melting can capture the empirically observed features of the so-called Østrem curve (a plot of the melt rate as a function of debris depth). Specifically, we show that the turning point in the Østrem curve can be caused by two distinct mechanisms: the increase in the proportion of ice that is debris-covered and/or a reduction in the evaporative heat flux as the debris layer thickens. This second effect causes an increased melt rate because the reduction in (latent) energy used for evaporation increases the amount of energy available for melting. Our model provides an explicit prediction for the melt rate and the temperature distribution within the debris layer, and provides insight into the relative importance of the two effects responsible for the maximum in the Østrem curve. We use the data of Nicholson and Benn (2006) to show that our model is consistent with existing empirical measurements.
In 2006, the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards recommended a 5-Minute Protocol as a brief screening instrument for vascular cognitive impairment (VCI). We report demographically adjusted norms for the 5-Minute Protocol and its relation to other measures of cognitive function and cerebrovascular risk factors. We performed a cross-sectional analysis of 7199 stroke-free adults in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study on the NINDS-CSN 5-Minute Protocol score. Total scores on the 5-Minute Protocol were inversely correlated with age and positively correlated with years of education, and performance on the Six-Item Screener, Word List Learning, and Animal Fluency (all p-values <.001). Higher cerebrovascular risk on the Framingham Stroke Risk Profile (FSRP) was associated with lower total 5-Minute Protocol scores (p <.001). The 5-Minute Protocol also differentiated between participants with and without confirmed stroke and with and without stroke symptom histories (p <.001). The NINDS-CSN 5-Minute Protocol is a brief, easily administered screening measure that is sensitive to cerebrovascular risk and offers a valid method of screening for cognitive impairment in populations at risk for VCI. (JINS, 2014, 20, 1–12)
Hoarding disorder is typified by persistent difficulties discarding possessions, resulting in significant clutter that obstructs the individual's living environment and produces considerable functional impairment. The prevalence of hoarding disorder, as defined in DSM-5, is currently unknown.
To provide a prevalence estimate specific to DSM-5 hoarding disorder and to delineate the demographic, behavioural and health features that characterise individuals with the disorder.
We conducted a two-wave epidemiological study of 1698 adult individuals, originally recruited via the South East London Community Health (SELCoH) study. Participants screening positively for hoarding difficulties in wave 1, and who agreed to be re-contacted for wave 2 (n = 99), underwent in-home psychiatric interviews and completed a battery of self-report questionnaires. Current DSM-5 diagnoses were made via consensus diagnostic procedure.
In total, 19 individuals met DSM-5 criteria for hoarding disorder at the time of interview, corresponding to a weighted prevalence of 1.5% (95% CI 0.7–2.2). Those with hoarding disorder were older and more often unmarried (67%). Members of this group were also more likely to be impaired by a current physical health condition (52.6%) or comorbid mental disorder (58%), and to claim benefits as a result of these issues (47.4%). Individuals with hoarding disorder were also more likely to report lifetime use of mental health services, although access in the past year was less frequent.
With a lower-bound prevalence of approximately 1.5%, hoarding disorder presents as a condition that affects people of both genders and is associated with substantial adversity.